Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits.

Abstract

BACKGROUND:

Among strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic high-density lipoprotein (sHDL).

METHODS:

New Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into 2 protocols: (1) a single-dose study, where rabbits were treated with a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200 mg/kg) or with Placebo; (2) a multiple-dose study, where 4 groups of rabbits were treated 5 times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by intravascular ultrasound. Blood was drawn from rabbits for biochemical analyses and cholesterol efflux capacity evaluation.

RESULTS:

In both protocols, atheroma volume in the Placebo groups increased between the first and the second intravascular ultrasound evaluation. A stabilization or a slight regression was instead observed vs baseline in the TN-sHDL-treated groups (P < 0.005 vs Placebo after infusion). TN-sHDL treatment caused a sharp rise of plasma-free cholesterol levels and a significant increase of total cholesterol efflux capacity. Histologic analysis of carotid plaques showed a reduced macrophage accumulation in TN-sHDL-treated rabbits compared with Placebo (P < 0.05).

CONCLUSIONS:

Our results demonstrate that acute and subacute treatments with TN-sHDL are effective in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be related to a reduced intraplaque accumulation of inflammatory cells. Besides recent failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic option for the reduction of cardiovascular risk.

• Authors: Cinzia Parolini, Maria Pia Adorni, Marco Busnelli, Stefano Manzini, Eleonora Cipollari, Elda Favari, Paolo Lorenzon, Giulia S Ganzetti, Juergen Fingerle, Franco Bernini, Giulia Chiesa
• Journal: The Canadian journal of cardiology (Can J Cardiol) Vol. 35 Issue 10 Pg. 1400-1408 (10 2019) ISSN: 1916-7075 [Electronic] England
• PMID: 31495683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein A-I
• Lipoproteins, HDL
• Pharmaceutical Preparations

Topics

• Animals
• Apolipoprotein A-I (administration & dosage)
• Hypercholesterolemia (complications)
• Infusions, Intravenous
• Lipoproteins, HDL (administration & dosage)
• Male
• Pharmaceutical Preparations
• Plaque, Atherosclerotic (etiology, prevention & control)
• Rabbits
• Random Allocation